Avaliação da cardiotoxicidade da doxorrubicina em cães – estudo piloto
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2017
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A doxorrubicina, é um potente agente antineoplásico, pertencente a uma das
principais classes de quimioterápicos utilizadas em oncologia, as antraciclinas. Este fármaco
apresenta atividade antitumoral contra uma grande variedade de neoplasias, tais como,
linfoma, sarcomas e carcinomas, no entanto, o seu uso é condicionado pela possível
ocorrência de cardiotoxicidade.
O mecanismo cardiotóxico da doxorrubicina ainda é controverso, no entanto, pensase
que está relacionado com um aumento do stress oxidativo no miocárdio, devido, sobretudo,
à formação de espécies reativas de oxigénio e indução de peroxidação lipídica nas células
cardíacas. A cardiotoxicidade induzida pela doxorrubicina manifesta-se de forma semelhante
à cardiomiopatia dilatada, num processo que depende da dose total cumulativa administrada.
Neste estudo, pretendi avaliar a presença de cardiotoxicidade em cães com diferentes
neoplasias, sujeitos a quimioterapia com doxorrubicina. Para o efeito, foram realizados
controlos de parâmetros ecocardiográficos e de biomarcadores cardíacos, durante 5 estádios
de administração de doxorrubicina.
Os resultados do estudo não foram sugestivos de ocorrência de cardiotoxicidade,
porém, um aumento da concentração de troponina I, com maior relevância no final do
protocolo, pareceu sugerir alguma contribuição da doxorrubicina na lesão do miocárdio.
Devido ao constrangimento associado às perdas de seguimento, frequentemente
implícitas na especialidade oncológica, não foi possível obter um tamanho de amostra ideal,
pelo que as conclusões retiradas deste estudo são limitativas.
Pretende-se, com este estudo, alertar para a importância de uma prevenção e controlo
frequentes da função cardíaca em animais tratados com este fármaco cardiotóxico. Apesar de
a cardiotoxicidade não ser tão frequente em cães, devido a uma menor agressividade dos
protocolos quimioterápicos e a um maior controlo das doses cumulativas utilizadas, creio que
é fundamental apostar na prevenção, de forma a assegurar um diagnóstico precoce de
cardiotoxicidade, ou até mesmo, de patologias cardíacas ocultas ou envolvimento cardíaco de
origem neoplásica, os quais, podem contribuir para um agravamento da saúde de cada
paciente.
Doxorubicin is a potent antineoplastic agent, belonging to one of the major classes of chemotherapeutic drugs used in oncology, the anthracyclines. Doxorubicin exerts antitumor activity against a wide variety of neoplasms, such as lymphoma, sarcomas and carcinomas, however, its use is conditioned by the possible occurrence of cardiotoxicity. The cardiotoxic mechanism of doxorubicin is still controversial, however, it is thought to be related to an increase in oxidative stress in the myocardium, mainly due to the generation of reactive oxygen species and lipid peroxidation, in cardiac cells. The cardiotoxicity induced by doxorubicin manifests itself in a similar way to dilated cardiomyopathy, in a process that depends on the cumulative total dosage administered. In this study, I intended to evaluate the presence of cardiotoxicity in dogs with different neoplasms, undergoing doxorubicin chemotherapy protocols. For this purpose, controls of echocardiographic parameters and cardiac biomarkers were performed during 5 stages of doxorubicin administration. Results of this study were not suggestive of cardiotoxicity, however, a consistent increase in plasma cardiac troponin I, with greater relevance at the end of the protocol, suggested some contribution of doxorubicin in myocardial injury. Because of the constraint associated with loss to follow-up, often implied in medical oncology, it was not possible to obtain an ideal sample size, so the conclusions drawn from this study are limiting. With this study, I pretend to alert to the importance of frequent prevention and control of cardiac function, in animals treated with this cardiotoxic drug. Although cardiotoxicity is not so frequent in dogs, due to the lower aggressiveness of chemotherapy protocols and a greater control of the cumulative doses, I believe that it is fundamental to focus on prevention in order to ensure an early diagnosis of cardiotoxicity, or even occult cardiac pathologies or cardiac involvement of neoplastic origin, which can contribute to a worsening of the health of each patient.
Doxorubicin is a potent antineoplastic agent, belonging to one of the major classes of chemotherapeutic drugs used in oncology, the anthracyclines. Doxorubicin exerts antitumor activity against a wide variety of neoplasms, such as lymphoma, sarcomas and carcinomas, however, its use is conditioned by the possible occurrence of cardiotoxicity. The cardiotoxic mechanism of doxorubicin is still controversial, however, it is thought to be related to an increase in oxidative stress in the myocardium, mainly due to the generation of reactive oxygen species and lipid peroxidation, in cardiac cells. The cardiotoxicity induced by doxorubicin manifests itself in a similar way to dilated cardiomyopathy, in a process that depends on the cumulative total dosage administered. In this study, I intended to evaluate the presence of cardiotoxicity in dogs with different neoplasms, undergoing doxorubicin chemotherapy protocols. For this purpose, controls of echocardiographic parameters and cardiac biomarkers were performed during 5 stages of doxorubicin administration. Results of this study were not suggestive of cardiotoxicity, however, a consistent increase in plasma cardiac troponin I, with greater relevance at the end of the protocol, suggested some contribution of doxorubicin in myocardial injury. Because of the constraint associated with loss to follow-up, often implied in medical oncology, it was not possible to obtain an ideal sample size, so the conclusions drawn from this study are limiting. With this study, I pretend to alert to the importance of frequent prevention and control of cardiac function, in animals treated with this cardiotoxic drug. Although cardiotoxicity is not so frequent in dogs, due to the lower aggressiveness of chemotherapy protocols and a greater control of the cumulative doses, I believe that it is fundamental to focus on prevention in order to ensure an early diagnosis of cardiotoxicity, or even occult cardiac pathologies or cardiac involvement of neoplastic origin, which can contribute to a worsening of the health of each patient.
Descrição
Orientação : Luís Lima Lobo ; co-orientação : Joaquim Henriques
Palavras-chave
MESTRADO INTEGRADO EM MEDICINA VETERINÁRIA, MEDICINA VETERINÁRIA, VETERINÁRIA, CÃES, MEDICAMENTOS, ECOCARDIOGRAFIA, FARMACOLOGIA VETERINÁRIA, VETERINARY MEDICINE, DRUGS, DOGS, ECHOCARDIOGRAPHY, VETERINARY PHARMACOLOGY, DOXORRUBICINA, DOXORUBICIN, CARDIOTOXICIDADE, CARDIOTOXICITY